1995 Senate Cancer Coalition Hearing on Genetic Testing

National Human Genome Research Institute

National Institutes of Health
U.S. Department of Health and Human Services


Senate Cancer Coalition Hearing on Genetic Testing

Statement of Francis S. Collins, M.D., Ph.D., Director
National Center for Human Genome Research

September 29, 1995

Overview of the Human Genome Project

Senator Mack, Senator Feinstein, and members of the Senate Cancer Coalition, it is my pleasure to appear before you today as the Director of the National Center for Human Genome Research (NCHGR) of the National Institutes of Health (NIH) and to have the opportunity to talk with you about the Human Genome Project and some of the critical issues surrounding genetic testing, particularly as it relates to cancer.

The Human Genome Project is a historic 15-year research endeavor with the goal of producing detailed maps of the 23 pairs of human chromosomes and sequencing the 3 billion nucleotide bases that make up the human genome. The primary mission of the project is to develop research tools -- genetic and physical maps, DNA sequence information, and new technology -- to allow researchers to find and analyze genes quickly and efficiently. The project thus far has been successful in meeting or exceeding the goals outlined in its original plan. As we celebrate the Human Genome Project's fifth birthday this fall, we are pleased to note that the genetic map is complete, the chromosome physical maps are within 18 months of completion, and the thrust to begin sequencing the entire human genome is getting underway. Further, we do not have to wait until the end of the project to reap its benefits; the information generated by the Human Genome Project is quickly disseminated to and utilized by researchers across the United States and throughout the world by placing all of the information in public electronic databases. Already this information is changing the way biomedical research and the practice of medicine are being conducted.

Applications of Genome Research

The tools of the Human Genome Project are leading to the discovery of an increasing number of genes associated with disease. An immediate spin-off of disease gene discovery will be the development of genetic tests that may indicate an individual's predisposition to disease. In the short term, this will allow the design of individual programs of preventive medicine, focusing on lifestyle changes and medical surveillance to reduce the risk of advanced illness. This may be particularly effective for cancer, where early detection is often the best chance for cure. Our knowledge will continue to grow about the function of these genes as researchers will have the ability to analyze at the molecular level the genetic causes of disease, and to associate specific gene alterations with an individual's risk for disease. Eventually, researchers will be able to develop new treatments for many of the diseases that result from malfunctions in our genes. However, there will often be a substantial lag time between our ability to offer a genetic test and the ability of researchers to understand the disease sufficiently well to develop new treatments and therapies.

For example, several recent gene discoveries are contributing to our understanding of the relationship between genetic alterations and cancer risk. We heard Brad Margus poignantly describe how his family has been affected by the fatal childhood disease, ataxia-telangiectasia (A-T), a rare hereditary neurological disorder. The recent discovery of this gene paves the way for more accurate diagnosis in the short term and the potential for effective treatments in the long term for children suffering from A-T. One of the interesting aspects of the discovery of the A-T gene is the indication that the gene may play a role in predisposition to certain cancers. Although the disease itself is rare, an estimated 2-3 percent of the U.S. population are carriers of the altered gene and have an increased risk for cancer. This suggests that 4-5 percent of all cancer (and 18 percent of breast cancer) in the American population may be associated with the A-T gene.

There have been many recent discoveries of genes associated with cancer, including genes for breast, ovarian and colon cancer. As we heard my colleague Dr. Klausner describe, there particularly have been significant developments surrounding genetics research and breast cancer. In September 1994, scientists isolated BRCA1, one of the first genes known to be associated with hereditary breast cancer. Based on studying high-risk families, scientists estimate that a woman who has a BRCA1 alteration has up to a 90 percent lifetime risk of developing breast cancer, and a 40-50 percent risk of ovarian cancer. Researchers have found over 50 different alterations in the BRCA1 gene in these high-risk families, and have just begun the complex task of studying the specific risk of cancer associated with each of these mutations.

Scientists have now found one specific BRCA1 alteration in several unrelated Jewish families with a family history of breast and/or ovarian cancer. These families were all of Ashkenazi, or Eastern European, descent. There was a significant announcement yesterday (September 28) from my own research group as data were released in Nature Genetics indicating that this particular alteration in the BRCA1 gene has now been found in about one percent of a group of Ashkenazi Jewish individuals, whose personal and family history of cancer was not known. This finding suggests that one in a hundred women of Ashkenazi descent may be at high risk of developing breast and/or ovarian cancer. Up to 16 percent of breast cancer and 39 percent of ovarian cancer in Jewish women under age 50 may be attributable to this single BRCA1 mutation. This offers the first evidence that a specific alteration in the gene is present at detectable levels not only in families at high risk for the disease, but also in a specific population group. With this information researchers can now design studies to understand better the role of BRCA1 in cancer, particularly for Ashkenazi Jewish women.

The NCHGR and the National Cancer Institute have already designed a clinical study that will include thousands of Ashkenazi Jewish men and women in the Washington metropolitan area to look at the relationship between this specific alteration and the risk of various cancers. The NIH has been pro-active in communicating this new finding to the Jewish community, health professionals and the public over the past few days.

I would like to stress that these data are still much too preliminary to recommend widespread BRCA1 testing until more is known about the specific risk of cancer associated with this mutation and the relative effectiveness of intensive surveillance and medical interventions. There is much more to be known before offering genetic tests should be contemplated outside of a research protocol setting. Numerous organizations, including the National Advisory Council for Human Genome Research, the National Breast Cancer Coalition and the American Society for Human Genetics, have stated that testing for cancer risk should only be carried out in the context of research protocols until more is known about the specific risk of cancer associated with genetic mutations, the technical and laboratory issues that need to be resolved, the relative effectiveness of various medical interventions, the appropriate counseling recommendations, and the possibility of genetic discrimination against those found to be at risk.

Overview of the Ethical, Legal and Social Implications Program

As an integral part of the Human Genome Project, the NCHGR and the Department of Energy (DOE) have each set aside a portion of their funding to anticipate, analyze, and address the ethical, legal, and social implications (ELSI) of the new advances in human genetics that human genome research has made possible. The goals of the ELSI program are to improve the understanding of these issues through research and education, to stimulate informed public discussion, and to develop policy options intended to ensure that genetic information is used for the benefit of individuals and society. The NCHGR ELSI program has focused on several high-priority areas raised by the most immediate potential applications of genome research:

  1. Ethical issues surrounding the conduct of genetics research.
  2. Responsible clinical integration of new genetic technologies.
  3. Privacy and fair use of genetic information.
  4. Professional and public education.

The NCHGR has taken two approaches to address the ELSI goals: 1) a research grant program on which NCHGR spends 5 percent of its annual budget and 2) an interagency working group, the NIH-DOE Joint Working Group on the Ethical, Legal and Social Implications of Human Genome Research (ELSI Working Group).

Testing and Counseling Initiatives

I would like to describe two initiatives underway at the NCHGR that are attempting to answer some of the crucial questions presented this morning. To examine issues surrounding the safe integration of genetic testing and counseling for cancer risk into clinical practice, the NCHGR has spearheaded a series of clinical research studies focused on testing and counseling for heritable breast, ovarian and colon cancer risks. The NCHGR, in conjunction with the National Cancer Institute, the National Institute of Nursing Research and the National Institute of Mental Health, has funded 11 research projects to study the psychological and social impact of cancer testing on individuals and their family members and to develop recommendations for approaches to genetic testing and counseling for cancer risk.

The investigators in these projects have formed a consortium to pool resources, reduce duplication of effort and increase coordination of some aspects of the studies. By gathering initial findings and results from the studies, it may be possible for the investigators to identify earlier emerging themes and recommendations. Some of the key aspects the investigators agreed to coordinate include: the use of a core set of evaluation tools to assist in the comparison of results from the studies; the identification of the key elements to be included in all consent forms used in the consortia studies; and a plan to develop specific recommendations for individuals who test positive for BRCA1 mutations. The two-to-three year projects were funded a year ago in the fall of 1994 and the first meeting of the Cancer Studies Consortium was held at the end of January 1995. The studies are well underway, and the investigators have developed draft recommendations for how to counsel patients and families who carry a BRCA1 mutation.

A second highly relevant initiative funded by the NIH is the Task Force on Genetic Testing (TFGT). The mission of the Task Force is to examine the strengths and weaknesses of current practices and policies relating to the development and delivery of safe and effective genetic tests and the quality of the laboratories providing the tests. The membership of the Task Force includes representatives from the biotechnology industry, the professional medical and genetics societies, the insurance industry, consumers, and the relevant federal agencies involved in the diffusion of new genetic tests. The Task Force is a subgroup of the ELSI Working Group and will report its findings through the ELSI Working Group and the National Advisory Council for Human Genome Research to the drectors of the NCHGR and the NIH.

The TFGT held its first meeting on April 13-14, 1995, and the group outlined the most crucial issues they will be addressing. The Task Force is concentrating on three areas:

  1. Scientific validation -- developing validation criteria for the sensitivity, specificity, and predictive value of the tests.
  2. Laboratory quality -- addressing the gaps in monitoring the quality of genetic tests.
  3. Education, counseling and delivery--providing ways to educate practitioners and consumers about the limitations and capabilities of current test technologies, including their predictive and interpretative value.

The rapid pace with which genes are being discovered and genetic tests are being developed indicates that the findings of the TFGT are urgently needed and will be crucial to the development of sound policies and practices for the introduction of new genetic tests.

Fair Use of Genetic Information

As our knowledge grows about individual susceptibility to disease, so too does the potential for discrimination and stigmatization based on the information contained in our genes. Of particular concern is the fear that we will lose our jobs or health insurance because we are shown to be at high risk for a particular disease. Denying individuals health insurance or employment based on genetic information will be an unfortunate deterrent to reaping the benefits of genetics research. Furthermore, we are all at risk for certain diseases, and as gene discoveries and genetic testing advances, we will have the opportunity to learn more about our individual susceptibilities. A health insurance system that uses this information to deny individuals coverage will be unworkable in the long term.

I would like to call your attention to the recent interpretation of the Americans with Disabilities Act, the federal legislation passed in 1990 that prohibits employment discrimination against persons with disabilities. Protection is provided under the ADA to an individual who has cancer or a history of cancer. However, it was not clear at that time if an individual who had a genetic predisposition to cancer was covered under the law. In March 1995, the U.S. Equal Employment Opportunity Commission (EEOC) released official guidance on the definition of the term "disability". The EEOC's guidance clarifies that protection under the ADA extends to individuals who are discriminated against in employment decisions based solely on genetic information about an individual. An employer who makes an adverse employment decision based on an individual's genetic predisposition to disease, whether because of concerns about insurance costs, productivity or attendance, is in violation of the ADA because the employer is regarding the employee as disabled. Issuance of the EEOC's guidance is precedent setting; it is the first federal protection against the unfair use of genetic information.

However, there are no Federal laws now in place to prevent health insurance companies from using genetic information to deny coverage. A recent analysis by Karen Rothenberg, Director of the Law and Health Care Program at the University of Maryland School of Law, has shown that several states are concerned about the use of genetic information and have passed legislation that protects individuals from being denied health insurance based on their genetic status. Several states now prohibit insurers from denying coverage based on genetic test results, and/or prohibit using this information to establish premiums, charge differential rates or limit benefits. A few of these states, including California, Florida and Oregon integrate protection against discrimination in insurance practices with privacy protections that prohibit insurers from requesting genetic information and from disclosing genetic information without authorization.

Recommendations

The ELSI Working Group has long been involved in discussions about the fair use of genetic information, particularly as it relates to health insurance. In 1993, the ELSI Working Group's Task Force on Genetic Information and Insurance concluded that, "Information about past, present or future health status, including genetic information, should not be used to deny health insurance coverage." Another important group recently formed is the National Action Plan on Breast Cancer (NAPBC), a public-private partnership established to address the research, education and policy issues in breast cancer. The NAPBC has identified the issue of genetic discrimination and health insurance as a high priority.

Building on their shared concerns, the ELSI Working Group and the NAPBC co-sponsored a workshop on July 11, 1995, to address the issue of genetic discrimination and health insurance. Consumers, researchers, federal and state government representatives, and insurance industry representatives came together with the members of these two groups to participate in the one day session. Based on the information presented at the workshop, the ELSI Working Group and the NAPBC developed the following recommendations for state and federal policy makers to protect against genetic discrimination:

  1. Health Insurance Access, Renewability, and Portability: Insurance providers should be prohibited from using genetic information, or an individual's request for genetic services, to deny or limit any coverage or establish eligibility, continuation, enrollment or contribution requirements.
  2. Health Insurance Affordability: Insurance providers should be prohibited from establishing differential rates or premium payments based on genetic information, or an individual's request for genetic services.
  3. Genetic Privacy: Insurance providers should be prohibited from requesting or requiring collection or disclosure of genetic information. Insurance providers and other holders of genetic information should be prohibited from releasing genetic information without prior written authorization of the individual. Written authorization should be required for each disclosure and include to whom the disclosure would be made.
  4. Definitions
    • "Genetic information" is information about genes, gene products or inherited characteristics, that may derive from the individual or a family member.
    • "Insurance provider" means an insurance company, employer, or any other entity providing a plan of health insurance or health benefits including group and individual health plans whether fully insured or self-funded.

Conclusion

The new advances in human genetics offer the promise that we will find new ways to fight some of the most devastating diseases that Americans suffer from today. We must ensure that our health care policies and practices relating to the introduction of new genetic tests and the subsequent use of genetic information keep pace with these significant new advances.

I would be pleased to answer any questions you may have. Thank you.

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Last Updated: March 16, 2012